VELUSETRAG HYDROCHLORIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H36N4O5S.ClH
Molecular Weight	541.103
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC(C)N1C(=O)C(=CC2=CC=CC=C12)C(=O)N[C@@H]3C[C@@H]4CC[C@H](C3)N4C[C@@H](O)CN(C)S(C)(=O)=O

InChI

InChIKey=BLIKSWRONBYRDD-ULYYJTHRSA-N

InChI=1S/C25H36N4O5S.ClH/c1-16(2)29-23-8-6-5-7-17(23)11-22(25(29)32)24(31)26-18-12-19-9-10-20(13-18)28(19)15-21(30)14-27(3)35(4,33)34;/h5-8,11,16,18-21,30H,9-10,12-15H2,1-4H3,(H,26,31);1H/t18-,19+,20-,21-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19691492 | https://www.ncbi.nlm.nih.gov/pubmed/18408918

Velusetrag (TD-5108) is a potent, selective high intrinsic activity serotonin 5-HT(4) receptor agonist. Velusetrag has achieved proof-of-concept in patients with chronic idiopathic constipation and was on phase II of clinical trial for the treatment of Alzheimer's disease and constipation, when studies were discontinued. In addition, velusetrag is on the phase II of clinical trial for the treatment of gastroparesis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
5-hydroxytryptamine receptor 4 8 Target ID: Q13639\|\|\|Q9NY73 Gene ID: 3360.0 Gene Symbol: HTR4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18408918	Agonist 2752		8.3 null [pEC50]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 278 Sources: https://clinicaltrials.gov/ct2/show/NCT01467726	Primary	Phase II 1147	Unknown Approved Use Unknown
Constipation 112 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19691492	Primary	Phase II 1147	Unknown Approved Use Unknown
Gastroparesis 9 Sources: https://clinicaltrials.gov/ct2/show/NCT02267525	Primary	Phase II 1147	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
Axon MedChem	2060	https://www.axonmedchem.com/product/2060
Compound Cloud	53297466
Compound Cloud	53297467
eMolecules	275088212	https://orderbb.emolecules.com/search/#?query=275088212
eMolecules	300875059	https://orderbb.emolecules.com/search/#?query=300875059
eMolecules	46024431	https://orderbb.emolecules.com/search/#?query=46024431
Molnova	M16300	https://www.molnova.com/en/serch-list.html?keywords=M16300
MolPort	MolPort-042-665-805	https://www.molport.com/shop/molecule-link/MolPort-042-665-805
MuseChem	I010011	https://www.musechem.com/product/I010011.html
Norris Pharm	NSZB-A152899
Ryan Scientific	101-94043	https://ryansci.com/products?q=101-94043&list_q=&search_type=exact

PubMed

Title	Date	PubMed
Phase II drugs under clinical investigation for the treatment of chronic constipation.	2014-11	24960333
Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly selective 5-HT(4) receptor agonist that has achieved proof-of-concept in patients with chronic idiopathic constipation.	2012-10-01	22959244
New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders.	2010-06	20408739
The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity.	2008-07	18415081
The serotonin signaling system: from basic understanding to drug development for functional GI disorders.	2007-01	17241888
Rationale for using serotonergic agents to treat irritable bowel syndrome.	2005-04-01	15790796
Serotonin: a mediator of the brain-gut connection.	2000-10	11051338
Signal transduction pathways for serotonin as an intestinal secretagogue.	1997-10	9366057
Participation of 5-HT3, 5-HT4, and nicotinic receptors in the peristaltic reflex of guinea pig distal colon.	1996-11	8944700

Patents

Sample Use Guides

In Vivo Use Guide

5, 15, 30 or 50 mg Velusetrag (single and 6-day dosing)

Route of Administration: Oral

In Vitro Use Guide

In all in vitro assays, TD-5108 was a high intrinsic activity agonist, unlike tegaserod, mosapride, and cisapride which, in the majority of test systems, had lower intrinsic activity. TD-5108 had high affinity (pK (i) = 7.7) and selectivity (> or =25-fold) for h5-HT(4(c)) receptors over other biogenic amine receptors. TD-5108 was >500-fold selective over other 5-HT receptors (including h5-HT(2B) and h5-HT(3A)) and, at 3 uM, had no effect on human ether-à-go-go-related gene K+ channels.

Name

Type

Language

VELUSETRAG HYDROCHLORIDE

Official Name

English

3-QUINOLINECARBOXAMIDE, 1,2-DIHYDRO-N-((3-ENDO)-8-((2R)-2-HYDROXY-3-(METHYL(METHYLSULFONYL)AMINO)PROPYL)-8-AZABICYCLO(3.2.1)OCT-3-YL)-1-(1-METHYLETHYL)-2-OXO-, MONOHYDROCHLORIDE

Preferred Name

English

VELUSETRAG HCL

Common Name

English

N-[(1R,3R,5S)-8-{(2R)-2-Hydroxy-3-[methyl(methylsulfonyl)amino]propyl}-8-azabicyclo[3.2.1]oct-3-yl]-1-(1-methylethyl)-2-oxo-1,2-dihydroquinoline-3-carboxamide hydrochloride

Common Name

English

VELUSETRAG HYDROCHLORIDE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66880